Neural modulation system

ABSTRACT

A neural modulation system includes neural encoder in a patient-external device. The neural encoder converts input signals into a neural stimulation pattern and wirelessly transmits the neural stimulation pattern to a patient-internal device. The patient internal device includes a flexible substrate and a two dimensional array of neural probes disposed on the flexible substrate. Each neural probe includes an array of magnetic neural stimulators and/or an array of neural sensors along with probe addressing circuitry that allow for addressing the magnetic neural stimualtors and/or neural sensors. Control circuitry in the implantable device controls activation of the magnetic neural stimulators and/or neural sensors according to the neural stimulation pattern via the probe addressing circuitry.

TECHNICAL FIELD

This disclosure relates generally to a neural modulation system and tomethods and devices related to a neural modulation system.

RELATED PATENT DOCUMENTS

This patent application is related to commonly owned and concurrentlyfiled U.S. patent application Ser. No. 15/616,479 having the title“IMPLANTABLE NEURAL MODULATION DEVICE” and U.S. patent application Ser.No. 15/616,496 having the title “IMPLANTABLE NEURAL PROBE” both of whichare incorporated herein by reference.

BACKGROUND

Neural modulation can be used in prostheses to compensate for reducedfunction. For example, visual prosthetics that use neural modulation canimprove visual acuity for many of the approximately 285 million peopleworldwide who are visually impaired.

SUMMARY

Some embodiments are directed to a neural modulation system. The systemincludes a patient-external device that comprises a neural encoderprogrammed to convert input signals into a neural stimulation patternthat is wirelessly transmitted to a patient-internal device configuredto be disposed within a cranium of a patient. An implantable neuralsubsystem is coupled to the patient internal device. The implantalbeneural subsystem includes a flexible substrate and a two dimensionalarray of neural probes disposed on the flexible substrate. The neuralprobes are configured to stimulate and/or sense neurons. Each neuralprobe includes an array of magnetic neural stimulators and/or an arrayof neural sensors. The implantable neural subsystem includes probeaddressing circuitry that allows the magnetic neural stimualtors and/orneural sensors to be addressed. Control circuitry controls activation ofthe magnetic neural stimulators and/or neural sensors according to theneural stimulation pattern via the probe addressing circuitry.

According to some aspects, the neural modulation system is a visionprosthesis system and the input signals are derived from a camera.

Some embodiments are directed to a method for restoring vision. Camerasignals are generated in response to an image. The camera signals aremapped to a neural stimulation pattern that represents the image. Theneural stimulation pattern is wirelessly transmitted to abody-implantable device that includes an array of magnetic neuralstimulators. The neurons of the visual cortex of he patient aremagnetically according to the neural stimulation pattern.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a diagram that illustrates intracortical layers;

FIG. 1B shows functional system components of the vision prostheticsystem in accordance with some embodiments;

FIG. 1C is a block diagram of a visual prosthetic system in accordancewith some embodiments;

FIGS. 2A and 2B respectively provide front and back views of a personwearing the visual prosthetic system in accordance with someembodiments;

FIGS. 3A and 3B respectively show portions of the patient-externaldevice, the patient-internal device, and the flexible membrane withneural probes contacting the visual cortex in accordance with someembodiments;

FIG. 4 shows in more detail the patient-internal device of the visualprosthetic system in accordance with some embodiments;

FIG. 5 is a block diagram that shows the circuitry of the internalportion of the visual prosthetic system of FIG. 1C in more detail;

FIGS. 6A through 6D illustrate fabrication of a neural probe inaccordance with some embodiments;

FIG. 7A is a scanning electron microscope (SEM) image of a micro-coilstimulator (less than 1 mm in diameter) encapsulated in Teflon by apatterned mold process in accordance with some embodiments;

FIG. 7B is a SEM image of a micro-coil stimulator (less than 1 mm indiameter) encapsulated in the electronics packaging polymer DEXTER HYSOL6511 in accordance with some embodiments;

FIG. 8 illustrates a stress-engineered subassembly that allows forrolling of the flexible substrate to form a probe in accordance withsome embodiments;

FIGS. 9A and 9B respectively show a flat flexible membrane that includeselectronic circuitry and electrically conductive wiring disposed thereonand the flexible membrane after it is rolled up as a neural probe inaccordance with some embodiments;

FIG. 9C shows a 120 μm diameter polyimide membrane suitable for a neuralprobe in accordance with some embodiments;

FIG. 9D shows a 350 μm diameter polyimide membrane suitable for a neuralprobe in accordance with some embodiments;

FIG. 10 is an image of a 3D coil which is suitable for use as a neuralstimulator in accordance with some embodiments;

FIG. 11 is a top view of a layout of four tethered elastic membersbefore release in accordance with some embodiments;

FIG. 12 is a top view detail of a raised mechanical stop on a contactpad in accordance with some embodiments;

FIG. 13 is a cross section along line 3-3 of the layout of FIG. 11;

FIG. 14 is a top view of a layout of five mid-air elastic member pairsbefore release in accordance with some embodiments;

FIG. 15 is a partial perspective view of the member pairs of FIG. 14during release;

FIG. 16 is a partial perspective view of the tethered elastic members ofFIG. 11 after release and formation of coil structures;

FIGS. 17 and 18 are top views of alternate elastic member tips inaccordance with some embodiments;

FIG. 19 is a top view of an alternate layout of four elastic membersbefore release in accordance with some embodiments;

FIGS. 20 and 21 are top views of a bi-directional elastic member layoutin accordance with some embodiments;

FIG. 22 is a top view of yet another alternate layout of four elasticmembers before release in accordance with some embodiments;

FIG. 23 shows a probe supporting an array of stimulation micro-coilsinterweaved with an array of neural sensors in accordance with someembodiments;

FIG. 24A is a graph showing the electric field gradient (log plot) of 3Dcoils in accordance with some embodiments vs. an equivalent planar coil;

FIG. 24B is a graph showing the penetration depth for a 3D coil as afunction of current;

FIG. 25A shows micro-coil addressing in accordance with someembodiments;

FIG. 25B shows coil driver circuitry configured to drive a micro-coil inaccordance with some embodiments;

FIG. 26A illustrates the magnetic field created by a single loop coil;

FIG. 26B illustrates the magnetic field created by a multi-loop coil;

FIG. 27 illustrates manipulation of the field strength of the electricfield at a selected location by approximately adding the linear vectorsof the individual fields in accordance with some embodiments;

FIG. 28A illustrates an algorithm suite that provides a general neuralinterface platform that supports the therapeutic vision prostheticsystem in accordance with some embodiments; and

FIG. 28B is a diagram that illustrates methods implemented by the visionprosthetic system to calibrate the neural stimulation so as to simulatevision in a visually impaired patient in accordance with someembodiments.

The figures are not necessarily to scale. Like numbers used in thefigures refer to like components. However, it will be understood thatthe use of a number to refer to a component in a given figure is notintended to limit the component in another figure labeled with the samenumber.

DETAILED DESCRIPTION

Embodiments disclosed herein are directed to a neural prosthetic systemand to related devices and methods. According to some embodiments, theprosthetic system magnetically stimulates neurons within the brain torestore body functionality. In the illustrated example, a visualprosthetic system magnetically stimulates neurons within the visualcortex to simulate sight for visually impaired people. Neural activationsignals produced in response to the magnetic neural stimulation aresensed and the sensed neural activation is used to adapt the magneticstimulation to achieve the desired visual functionality. Although theexample of a visual prosthetic are described herein, it will beappreciated that other applications involving brain stimulation are alsopossible using the systems, devices, and methods discussed herein.

The therapeutic goal of the visual prosthetic system is to restore atleast some level of vision to the blind, particularly those who havesuffered trauma of the eye or diseases such as glaucoma, maculardegeneration, and retinitis pigmentosa—by implanting a prosthetic intothe primary visual cortex (V1) of blind subjects. The intracorticallayers of the primate visual cortex are illustrated in FIG. 1A.Prostheses that target the retina or other early visual centers cantreat only a few forms of blindness. However, a system as discussedherein that targets the cortex is useful for a much wider range ofvisual deficits, up to and including traumatic loss of the eye.

According to some embodiments, the visual prosthetic system discussedherein can target about 100,000 distinct visual neurons. Tiny, spatiallyasymmetric magnetic fields can be scaled to activate only singleneurons, or to activate larger populations in the immediate surroundingsof each coil. The asymmetric fields have a strong component orientedperpendicularly to the cortical surface and a much weaker component thatis parallel.

The approach discussed herein involves the consideration thatperpendicularly-oriented pyramidal neurons can be activated while axonsof passage and other horizontally-oriented processes will not. Pyramidalneurons are an attractive target because they are the major excitatoryneurons of the cortex and their output serves as the primarycommunication signal with all other regions of the cortex, as well asother brain centers. Avoiding the axons of passage and other horizontalprocesses further ensures that activation remains confined to narrowregions around each coil, instead of the unwanted spread of activationthat arises from the indiscriminate activation of axons that occurs withelectrodes. The high permeability of magnetic fields offers increasedreliability over other devices (i.e., coils are not susceptible toencapsulation or other biological responses to implantation).

It can be desirable for the prosthetic system to replicate key elementsof physiological signaling. Each probe (the part of the prostheticinserted into the cortex) can be capable of selectively activating thepyramidal neurons of individual cortical layers, (e.g., 2,3, 5 and 6 aswell as the granule cells of layer 4). The granule cells are the inputneurons of the cortex and their activation will in turn utilize thedownstream synaptic circuitry. This will result in closer matches tophysiological signaling in each type of (downstream) pyramidal cell.However, even with the high level of selectivity that can be achievedwith micro-coils, the neural patterns that arise in each type ofpyramidal neuron are not likely to perfectly match physiologicalpatterns. Thus, the ability to independently activate each type ofpyramidal neuron can be used to bring the resulting neural signal (ineach PN) more in line with its normal physiological response. Whileperfect matches to physiological signaling may not be possible, theability to match certain important elements of such signaling is likelyto greatly improve the quality of elicited vision.

In addition to the ability of the prosthetic system to stimulate up to100,000 or more neurons independently, the system may also record from(sense) at least 1 million cortical neurons. Implanted tetrodes cancapture signals from thousands of neurons simultaneously, therebygreatly reducing the number of penetrations by the probes that need tobe made into the cortex. The ability to simultaneously read and writeneural activity offers tremendous opportunities for unraveling keyelements of cortical function, but will also be highly useful forimproving the efficacy of the prosthetic. The ability to read theneuronal responses that arise in response to stimulation will providefeedback on the level of similarity between induced and physiologicalpatterns, and lead to enhanced stimulation strategies that producematches that are within specified design parameters.

Simultaneous stimulation and recording with the same device poses aconsiderable challenge because the electrical artifacts induced by thestimulus waveform can complicate the elicited neural response.Fortunately, the tiny magnetic fields that arise from the magnetic coilsproduce very small artifacts that do not significantly impede theability to detect spikes. For this application, the design criteria fora neural implant in accordance with some embodiments is summarizedbelow.

FIG. 1B shows functional system components of the vision prostheticsystem in accordance with some embodiments. The functional componentsare grouped into four modules: the core electronics module 181, thetransducer module 182, the power management module 183, and the neuralencoder module 184. The neural encoder module 184 resides outside thebrain, and be disposed on a headband head band, its main role being toprovide the more intensive (and heat generating) signal processingcomputations.

The neural encoder module 184 is programmed to map camera signalsresponsive to an image to neural stimulation signals that will cause thepatient to “see” the image. The neural encoder module includes a brainto digital component that receives information from neural sensorsignals and a digital to brain component that sends pattern informationfor the neural stimulation to the internal electronics core module. Thealgorithms suite maps the camera signals to the neural stimulationpattern.

The transducer module 182, which is physically wired to the coreelectronics module 181, contains the tetrode array and micro-coils on acommon substrate for reading and writing to neurons, respectively. Theelectronics module 181 is responsible for current injection in themicro-coils, acquisition of data from the read submodule, telemetry, anddistribution of power to the sub-modules. The electronics module 181 canbe wirelessly powered from a head band. To ensure that the implanteddevice stays within thermal safety limits, the system includes a powermanagement module 183.

The transducer module 182 comprises a flexible substrate comprising anarray of probes, e.g. cylindrical probes, as described in greater detailherein. The probes include tetrodes for sensing neural activity andmicro-coils for stimulating neurons. In some embodiments, the surface ofthe probe consists of alternating structures of tetrode (sensing) andmicro-coil (stimulating) structures.

The prosthetic systems illustrated herein provide an adaptive neuraltransducer technology platform for high density operations that readneural signals and/or stimulate neurons. Systems described herein arecapable of real-time data processing and dynamic control of brainfunctions. The cortical-based visual prosthetic provides arepresentative therapeutic application. In some embodiments, the visualprosthetic can sense at least 10⁶ neurons and can stimulate at least 10⁵neurons, although other numbers of neurons sensed and/or stimulated arealso possible. According to some embodiments, intracortical layers 2,3,and 5,6 may be stimulated, the cortical area stimulated can be betweenabout 1.5 to about 2.5 cm², e.g., about 2 cm², with a resolution ofbetween about 15 to about 25 μm, e.g., 20 μm in some embodiments. Insome embodiments, vertically oriented neurons (VONs) may be selectivelystimulated. The prosthetic is capable of generating patterns of neuralactivity leading to predictable visual perception in primates. Thevisual prosthetic system described herein is configured to 1) implementsafe, long-term, high-density, and high-selectivity sense/stimulationinterfaces, 2) process hierarchical data at scale and in real-time, and3) adaptively interact with cortical function.

Previous neural interfaces using in human clinical studies were largelybased on electrical sensing (also referred to as “recording”) andelectrical stimulation. For neural sensing, localized, multi-shankprobes allow for simultaneous sensing of closely spaced neuronpopulations and for the determination of the spatial relationships amongisolated single neurons. Embodiments described herein includeimplementation of electrical sensing which causes reduced or minimaldamage to cortical structures.

Whereas electrical neural sensing is useful, neural stimulation byelectrical signals is suboptimal. Electrical stimulation is notselective, damages tissue, and is known to trigger immune responses. Toovercome these limitations, the visual prosthetic disclosed hereinemploys a magnetic stimulation approach based on micro-coils. Magneticstimulation offers enhancements over electrical stimulation in that itis highly selective, is able to penetrate biological tissues (e.g., isnot impacted by biological encapsulation), has constant stimulationefficacy over time, and is a contactless and safe method. In general,the coils may have any suitable geonetry, e.g., planar or non-planarcoils. In the disclosed embodiments, a three dimensional (3D) micro-coilgeometry allows reduced current injection when compared to a planarcoil. For example, the current injection of the 3D micro-coil may bereduced about 100 times when compared to the planar coil, reducing thetotal power dissipation of 100 k coils from 1 Watt to less than about 10mW. In addition, 3D micro-coils provide more degrees of freedom tocreate spatially-asymmetric fields, and to confine activation to highlyfocused regions when compared to flat magnetic coils and/or electricalstimulation approaches. The 3D micro-coils can be used to implement afield manipulation method involving focused magnetic field (FMS), thatenables more localized stimulations, better depth control, and complexstimulation patterns (via beam shaping and beam steering) when comparedto flat magnetic coils and/or electrical stimulation approaches. Forexample, in some implementations an array of 3D micro-coils may bedesigned to have a sub-neuronal resolution of less than about 25 μm.

Embodiments of the visual prosthetic disclosed herein uses a flexibleelectronics backplane with thin film transistors (TFTs) switches thatsupport massive multiplexing of the neural sensed signals and neuralstimulation signals. In these embodiments, the role of the flexibleelectronics platform is two-fold: it minimizes tissue damage throughbetter mechanical flexibility, and provides multiplexing at the neuralsense and/or stimulation sites. The use of TFTs for multiplexing canreduce the number data lines that must be routed upstream to detectionelectronics to a few hundred of data lines. The TFTs also allowlower-level logic circuitry to be disposed locally on the neural probesthat include the neural sensors and neural stimulators.

Sensing and/or stimulating neurons using dense array of sensing orstimulation transducers can be challenging. Power and heat constraintsare involved for such intensive on-board computation. To address thesechallenges, the electronics and algorithms of the visual prostheticsystem disclosed herein are partitioned between an implanted device anda patient-external wearable device that is wirelessly communicativelycoupled to the implanted device. Compression algorithms enabletransmission of data between the implanted and external devices via thebandwidth-limited wireless telemetry. The distribution of theelectronics and algorithms between the implanted device and the externaldevice enhances accuracy while reducing on-board power use and heatgeneration of the implanted device.

The algorithms initially used for stimulating the neurons can be derivedby high frequency sampling of neural signals produced by non-humanprimates with intact vision pathways at the intended stimulation areasan optionally areas farther down the vision pathway. The stimulatingalgorithms initially developed from the neural signals in non-humanprimates that are not blind can be subsequently refined for the patientusing the visual prosthesis system using machine learning based onfeedback signals from the patient's neural sensors. The machine learningis implemented until the stimulation produces the desired neural signalsand the algorithm is updated accordingly.

Turning now to FIG. 1C, there is shown a block diagram of acortical-based visual prosthetic system 100 in accordance with someembodiments. As previously discussed, the visual prosthetic system 100may have the capability of stimulating (writing to) at least 10⁵ neuronsand sensing (reading) at least 10⁶ neurons. The visual prosthetic system100 includes a patient-external first portion 101 disposed outside thepatient's body and a patient-internal first portion 102 configured to beimplanted within the skull of the patient. The patient-external portion101 includes a camera 105 and a patient-external electronic device 110.The patient-internal portion 102 includes a patent-internal device 120coupled to a flexible substrate 150 that supports addressing circuitryand an array of neural probes 140.

Image signals from the camera 105, which may be mounted on glasses orgoggles, are transferred to patient-external control electronics 110.The image signals are processed according to a vision algorithmimplemented by the patient-external electronic device 110 and/or thepatient-internal electronic device 120. The patient-external andpatient-internal electronic devices 110, 120 are communicatively coupledthrough a wireless communication channel 130 formed by internal andexternal electromagnetic coupling circuitry 131, 132. The visionalgorithm converts the image signals of the camera 105 into neuralstimulation control signals for controlling the stimulation micro-coilsof the neural probes.

The patient-internal electronic device 120 includes electronic circuitrydisposed within a suitable biocompatible housing that is fastened to theinterior surface of the patient's skull. The patient-internal device 120is coupled through the flexible membrane 150 to the neural probes 140which can be positioned to directly contact the visual cortex. Theneural probes 140 may include at least one sensor array 141 configuredto sense neural activity of the visual cortex and at least onestimulation micro-coil 142 array configured to stimulate the visualcortex. The flexible, biocompatible membrane 150 supports address linesthat select neural sensors and stimulators and data lines that carry thesensor and stimulation signals. The flexible substrate 150 may supportTFTs and/or other circuitry that provide for addressing the sensors 141and micro-coils 142 and carrying the sensor and stimulation signals fromthe internal device 120 to the sensors 141 and micro-coils 142.

The electronics of the patient-external device 110 and the camera 105are powered by a portable battery 160. The electronics of thepatient-internal device 120 and addressing electronics 143 (e.g., TFTsand related circuitry) of the neural probe 140 are powered by inductiveenergy transmitted from the patient-external inductive transmitting coil131 to the implanted inductive receiving coil 132. The current producedin the inductive coil 132 by the transmitted inductive energy isrectified and regulated in the power component 170 of thepatient-internal device 120. The power component 170 supplies power tothe patient-internal device 120, front end electronics 143, and probes140.

FIGS. 2A and 2B respectively provide front and back views of a personwearing the visual prosthetic system 100. FIGS. 3A and 3B respectivelyshow portions of the patient-external device 110, the patient-internaldevice 120, and the flexible membrane 150 with neural probes 140contacting the visual cortex.

FIG. 4 shows in more detail the patient-internal device 120 of thevisual prosthetic system 100. The patient-internal device 120 includeselectronics 421 contained within an enclosure 425 having a volume ofless than about 1 cm³ in some embodiments. In some configurations, theenclosure 425 may have a volume in a range of about 2 cm³ to about 0.5cm³. For example, the volume of the enclosure 425 may be less than about1 cm³ in some embodiments. The enclosure 425 containing the electronics120, flexible membrane 150, and neural probes 140 are configured to beimplanted within the skull of the patient and are made of suitablematerials for implantation. The flexible substrate 150 includes aproximal region 401 that includes an interface area 401 a configured toelectrically connect the flexible membrane 150 to the circuitry 421. Theflexible substrate 150 is mechanically coupled to the enclosure 425 atthe proximal region. A distal region 403 of the flexible membrane 150comprises the probes 140 and a center region 402 is disposed between theproximal region 401 and the distal region 402. As illustrated in FIGS.3B and 4, the electronics enclosure 425 is configured to be fastened tothe skull, e.g., by drilling and inserting screws, while the flexibleelectronics sheet 150 sits on top of the cortical layers with the probes140 penetrating the visual cortex.

In accordance with embodiments described herein, the flexible substrate150, the array of probes 140 and the thin film circuitry 143 foraddressing the probes 140 can be considered a “microsystem-on-plastic.”The transducers (micro-coils and sensor tetrodes) and thin filmtransistor (TFTs) addressing circuits are patterned on the flexiblesubstrate 150. After the components (sensors, micro-coils, andaddressing electronics) are deposited on the substrate 150, sections ofthe substrate 150 are rolled up to form the probes 140. The probes 140are located at the end of the flexible substrate 150 and are configuredto penetrate into the visual cortex (V1). The probes 140 are formed byrolling up sections of the flexible substrate that support thetransducers.

FIG. 5 is a block diagram that shows the circuitry of the internalportion 102 of the visual prosthetic system 100 in more detail. Asdepicted in FIG. 5, the internal portion 102 of the visual prostheticsystem 100 includes a plurality of neural probes 540, front endaddressing electronics 543, and a neural interface bus 545, all of whichare disposed on a flexible membrane. According to some implementations,the neural probes 540 include 103,680 encapsulated stimulus micro-coils542 a, b, c and 51,840 neural sensors (e.g., tetrodes) 541 a, b, corganized into an 18 by 18 array of 324 probes 540 a, b, c. In somearrangements, each probe 540 a, b, c comprises 320 micro-coils 542 a, b,c and 160 interleaved sensors 541 a, b, c that connect to a neuralinterface bus 545 through the front end electronics 543. According tosome implementations, the front end addressing electronics 543 comprisesa digital gate array 543 a, b, c corresponding to each probe 540 a, b,c. The digital gate array 543 a, b, c for the corresponding probe 540 a,b, c can connect either the 320 micro-coils 542 a, b, c or the 160sensor electrodes 541 a, b, c or both to the control circuitry 520.

The neural interface bus 545 may be configured to provide truebi-directional capability for any one or more of the probes 540 a, b, cin the probe array 540. The neural interface bus 545 connecting theprobes 540 a, b, c to the control electronics 520 comprises activationlines that include a 320-line neural stimulus bus 545 a, with a 10 bitstimulus address bus 545 b and a 6 line stimulus control bus 545 c. Thestimulus address bus 545 b and stimulus control bus 545 c, driven by thecore control module (CCM) 521 of the control circuitry 520 carry signalsthat select the set of one or more stimulation micro-coils 542 a, b, c,that are activated. The neural stimulus bus 545 a carries the signalthat drives the selected micro-coils 542 a, b, c.

The neural interface bus 545 also includes a 160 line neural acquisitionbus 545 f, with a 10 bit acquisition address bus 545 d and a 6 lineacquisition control bus 545 e. The acquisition address bus 545 d andacquisition control bus 545 e are driven by the core control module(CCM) 521 to select the set of one or more neural sensors 541 a, b, c,that are activated and the neural acquisition bus 545 f carries thesensor signal output by the sensor 541 a, b, c. The neural acquisitionbus 545 f is coupled to the analog to digital converter (ADC) 525 of thecontrol circuitry 520.

The control circuitry 520 controls the selection of the micro-coils 542a, b, c and/or neural sensors 541 a, b, c, as well as the waveforms ofthe stimulation signals used to activate the micro-coils 542 a, b, cand/or the signal conditioning of the sensor signals 541 a, b, c. Theneural stimulus bus 545 may be configured to operate in a time divisionmultiple access (TDMA) mode of operation with 200 μs time slots in whicheach probe's digital gate addressing array 543 a, b, c connects theprobe 540 a, b, c to the neural stimulation bus 545. This enables thecore control module 521 to generate a 100 μA pulse with a pulse width of167 μs and deliver it to any one or more of the 320 coils 542 a, b, c ofa probe 540 a, b, c. Both the current and the duration of the pulse maybe modified to increase selectivity or reduce latency for the associatedneuron. This configuration can stimulate the entire 103,680 coils 542 a,b, c in 64.8 ms, yielding a 15.4 frames per second refresh rate orapproximately 1.6 million neural stimulations per second.

The neural acquisition bus 545 f will normally operate in a timedivision multiple access (TDMA) mode of operation with 4 ms time slotsthat can capture the sensor signals 541 a, b, c generated by theindividually stimulated neurons. These sensor signals 541 a, b, c arethen shunted onto the bus 545 f through the probe's digital gateaddressing array 543 a, b, c where they are conditioned and converted todigital format in the ADCs 525 located in the control circuitry 520.This configuration enables the entire array of sensors 541 a, b, c toscan all 103,680 neurons within 1.3 seconds.

The CCM 521 directs the selection of probes 540 a, b, c to ensure theproper operation and response of the stimulated neurons. The probe array540 and front end electronics 543 can complete full bi-directionaltransactions with 1280 neurons in 12 ms. The CCM 521 may comprise aXilinx Spartan 6 low-power (XC6SLX35L) FPGA fabricated with a 65 nmprocess and contains configurable logic blocks that will operate at 1 Vand 5 MHz, thereby achieving ultra-low power and thermal signature. Theprocessing capability is more than adequate to simultaneously operatethe neural interface bus 545, and ADCs 525, as well as operate thecommunication link with the transceiver 522 and antenna 524.

The probe array 540 may comprise about 100 to about 500 probes, e.g.,about 324 probes (18×18 array), or other number of probes sufficient tostimulate about a 20 cm² region. The probes in the array 540 may bespaced apart by about 700 to about 800 μm, e.g., 750 μm to reduce damageto the brain. In some implementations, there may be about 160 electrodesand/or 320 coils per probe with 324 probes per probe array 540.

In some embodiments, the transceiver 522, which may comprise, forexample, a Qualcomm WCN3680B transceiver, is capable of up to 433 Mbpsdata upload speeds from the CCM 521 to the patient-external device withsub-ms latencies. The transceiver 522 can receive up to 5 to 6 GHztransmissions of RF energy and signal with 256-QAM encoding from thepatient-external device. The signal transmitted from thepatient-external device is received through an radio frequency (RF)electromagnetic coupling, which comprises one or more micro-stripantennas 524 that are designed to transmit and receive through the skulland surrounding tissue. The electromagnetic signal received by theantenna 524 is fed into a directional coupler 523, which splits off afirst portion of the received signal (power portion) to a rectifier 531and boost converter circuit that in turn charges a supercapacitor 532.The energy in the supercapacitor 532 can be converted and regulated toenable the operation of the CCM 521, transceiver 522, front endcircuitry 543, and neural probes 540. A second portion of the receivedsignal (communication portion) carries a communication signal and isdirected to the transceiver 522 for communication.

Regarding the signal power budget of the signal that links thepatient-external and patient-internal devices, the RF signal from thepatient-external transceiver is transmitted at a power level 27 dBm, andwould be attenuated by about 4 dB through the resonant RF couplingbetween the patient-external and patient-internal devices. Thus, theresulting 23 dBm signal would be split in the directional coupler 523into a near 23 dBm power signal, which would enter the rectifier 531.The communication signal enters the transceiver 522, where the receivesensitivity is −72 dBm, resulting in a 35 dB communication link margin.The uplink would be transmitted at −20 dBm, and be attenuated by about12 dB through the RF switch and resonant coupling between thepatient-internal and patient-external devices. The communication signalwould then enter the external device receiver at −32 dBm yielding a 40dB communication link margin. The data transmission bandwidth is 433Mbps, which is achieved by using an appropriate transceiver 522, such asthe WCN3680B 802.11ac from Qualcomm. In this architecture, the wideparallel neural stimulation bus 545 a and the distributed gate arrays543 a, b, c would allow the 320 neurons associated with each probe 540a, b, c to be stimulated by the 320 micro-coils 542 a, b, c, andsubsequently read by the 160 sensor electrodes 541 a, b, c. Thus, all324 probes 540 a, b, c, would be able to stimulate and read theassociated neurons in the time required to cycle the neuron bus to eachprobe. This would result in the bidirectional read-write of all 100,000+neurons addressed by the neural interface bus 545. For channelisolation, interlacing the stimulus and receiving transmission lines ofthe neural stimulus bus 545 a and neural acquisition bus 545 f,respectively, over a ground plane achieves about 80 dB of isolationbetween adjacent read channels from 300 Hz to 3 kHz, which insimulations has been determined to be the normal operating range of theneural acquisition bus 545 f. Thus, according to this particularexample, the power budget for the system can be less than about 120 mW.

The CCM 521 and the power management module 530 may be packaged togetherin a traditional hermetic package. Given the need to transmit RF datathrough the package, at least one face of the package may be ceramic.The package will also include metallic features to allow for hermeticwelding. The transducer module package, which includes the flexiblemembrane 550, front end circuitry 543, and probes 540 can be hermetic orsemi-hermetic. In some embodiments, the transducer module is expected tobe coated with a combination of parylene and silicon dioxide. Given theperformance requirements of the transducer module, this packagingstrategy is expected to provide sufficient protection from body fluids.

In lieu of the use of traditional hermetic packaging (e.g., ceramic andmetallic), an alternate packaging option for modules of thepatient-internal device may be polymer encapsulation. In particular,combining polymer encapsulants with different properties (i.e., epoxy,silicone, or parylene) can provide significant protection againstelectrical shorts, material leaching, and corrosion. All mechanicalpackages are designed to pass hermetic leak testing, e.g. perMIL-STD-883, or via visual inspection and soak testing.

FIGS. 6A through 6D illustrate fabrication of a neural probe inaccordance with some embodiments. The neural probe fabrication processincludes deposition of electronic components, including neural sensors,neural stimulators, and front end electronics in a probe area 655 of theflexible substrate 650, e.g., a polyimide membrane. As indicated in FIG.6A, in some embodiments, the neural sensors 641 and stimulators 642 areformed on a first surface 651 of the flexible substrate 650 and thefront end electronics 643 are formed on an opposing, second surface 652of the probe area 655 of the flexible substrate 650. When laid flat, theprobe area has a surface area of about 0.0048 cm² to about 0.032 cm².The probe area may contain about 250 to about 450 neural stimulatorsand/or about 250 to about 450 neural sensors. In some embodiments, theneural sensors 641 are disposed on the first surface 651 of the flexiblemembrane 650 and the micro coils and electronics are disposed on thesecond surface 652 of the flexible membrane 650. As previouslydiscussed, the neural sensors 641 may comprise tetrodes and the neuralstimulators 642 may comprise three dimensional micro-coils. In someembodiments, the front end electronics 643 may include TFTS used asswitches for selecting the neural sensors 641 and stimulators 642. Insome embodiments, the front end electronics 643 may comprise TFT-basedshift registers, logical circuits, and/or multiplexers, etc.

Before or after deposition of the sensors 641, stimulation coils 642,and electronics 643, the probe area 655 is detached from other areas ofthe flexible membrane 650 (except for a bridge). The probe area 655 maybe detached by laser or die cutting along a majority of the perimeter656 of the probe area 655. The probe area 655 of the flexible membrane650 is separated from the rest of the flexible membrane 650 at the cutperimeter 656 and remains attached to the rest of the flexible membrane650 by at least one uncut section of the perimeter, referred to hereinas a bridge 657 b. After deposition of components 641, 642, 643 in theprobe area 655 of the flexible membrane 650 and cutting the perimeter656, the flexible membrane 650 can be rolled up or folded to form athree dimensional probe 640. In some embodiments, after the probe area655 is rolled up, the neural sensors 641 are disposed on the exteriorsurface of the probe 640. The neural stimulators 642 and front endelectronics 643 are disposed on the interior surface of the probe 640such that the neural stimulators 642 and front end electronics 643 areprotected within the interior of the probe 640. In some embodiments,after the probe area 655 is rolled up, the neural sensors 641 and theneural stimulators 642 are disposed on the outer surface of the probe640. The front end electronics 643 are disposed on the inner surface ofthe probe 640 such that the front end electronics 643 are protectedwithin the interior of the probe 640. FIG. 6B illustrates the flexiblemembrane 650 as it is being rolled up into a probe 640. The exteriorsurface of the probe 640 comprises at least a portion of the firstsurface of the flexible substrate and the interior surface of the probe640 comprises at least a portion of the second surface of the flexiblesubstrate.

FIG. 6C shows the rolled up probe 640 attached by the bridge 657 b tothe rest of the flexible membrane 650. The probe 640 is oriented at anangle, e.g., about a 90 degree angle, to the plane of the rest of theflexible membrane 650 at the bridge 657 b and can penetrate the duramatter of the brain while being supported by the rest of the flexiblemembrane 650. FIG. 6D is a close up view of the external surface 651 ofthe probe 640 showing neural sensors 641 intermingled with neuraltransmitters 642. The external surface 651 of the probes 640 iscomprised of a periodic array of micro-coils 642 which are configured tostimulate the neurons of the visual cortex and tetrodes 641 which areconfigured to sense the neurons of the visual cortex.

The flexible membrane 650 provides a flexible electronics substrate. Theflexible membrane 650 may have a thickness between about 2 μm to about10 μm, e.g., in some embodiments, the flexible membrane 650 has athickness of about 4 μm. Despite being so thin, the flexible membrane650 has adequate strength to be self supporting. The rolled up probes640 may have a diameter of between 10 μm to 100 μm, e.g., the probes maybe about 30 μm in diameter in some embodiments. The probes 640 can havea length of about 1 mm to about 3 mm, or about 1.4 mm to about 2 mm, orabout 1.6 mm, for example. The probes 640 have a length that allowspenetration deep enough to reach intracortical layers 5 and 6.

Writing to neurons is accomplished by magnetic stimulation using thearray of micro-coils 642. Reading the neurons is achieved by sensingneural signals using the electrically-isolated tetrodes 641. The neuralsensors may be in contact with the visual cortex. In contrast, theneural stimulators need not be in direct contact with the visual cortex.

The tetrodes may be cylindrical patches about 2 to 10 μm in diameter, orsquare regions of about 2 to 5 μm by about 2 to 5 μm, and about 2 to 10μm tall. The tetrodes can have an area of about 25 μm, for example. Insome embodiments, the tetrodes 641 are about 5 μm in diameter and about5 μm tall. The tetrode sensors 641 and electronics 643 can be formedusing standard optical lithography.

The micro-coils 642 may be between about 10 μm to 30 μm or about 15 μmto about 25 μm in diameter and length. For example, in some embodiments,the micro-coils 642 may be about 20 μm in diameter and length, having anarea of about 400 μm².

The 3D micro-coils 642 can be formed using stress-engineered materialsas discussed in more detail below. According to some embodiments, the 3Dmicro-coils 642 comprise MoCr films which are sputter-deposited with abuilt-in stress gradient such that when patterned and released fromtheir substrate, they curl into a designed radius of curvature. Thescaffolds are then electroplated with copper to form highly conductivecoil windings. Coils of radius curvature of about 10-20 μm can befabricated by controlling parameters of beam length, width, thicknessand strain gradient and suitable as stimulation transducers for thevision prosthetic system.

There are a variety of options for coating the coils to ensurerobustness. FIGS. 7A and 7B show two methods of coating which result inrugged coils, allowing the coils to survive electronic die tests, suchas drops on hard surfaces from heights of over 1 m.

FIG. 7A is a scanning electron microscope (SEM) image of a micro-coilstimulator (less than 1 mm in diameter) encapsulated in Teflon by apatterned mold process. FIG. 7B is a SEM image of a micro-coilstimulator (less than 1 mm in diameter) encapsulated in the electronicspackaging polymer DEXTER HYSOL 6511.

The probe 640 can be rolled up by strain engineering. The polyimidemembrane supporting the sensors, stimulators, and electronics can berolled in about 30 to about 100 μm diameter cylinders using a bottom-upprocess, which is conceptually similar to the process used to producethe stressed metal coils as discussed below. Compared to top-downrolling the polyimide membrane using external forces (e.g., rolling byhand), a bottom-up process improves reproducibility and scalability.

FIG. 8 illustrates a stress-engineered subassembly 800 that allows forrolling of the flexible membrane to form a probe. The subassembly 800includes a substrate 810, wherein the substrate is rigid compared to themembrane 850. A release layer 820 comprising photoresist or othersuitable release material, is formed on the substrate 810. The materialof the flexible membrane 850 is disposed on the release layer 820. Theflexible membrane 850 includes a polyimide layer 851 and a hydrogellayer 852. When the release layer 820 is removed, e.g., by etching, thehydrogel layer 852 is configured to contract by de-swelling after thepolyimide 851 has been released from the rigid substrate 810.Contraction of the hydrogel layer 852 causes the flexible membrane 850including the polyimide membrane 851 to roll. The diameter of the rollis determined by the strain state in the flexible membrane 850 and itsthickness, which can be controlled by layer synthesis parameters andde-swelling conditions.

Thin film devices on rolled-up polymers have been fabricated withcontrolled and reproducible diameters ranging from 10 to 150 μm. Rollingof the polymer can be accomplished without substantial impact to thecomponents supported on the membrane.

FIGS. 9A and 9B respectively show a flat flexible membrane that includeselectronic circuitry and electrically conductive wiring disposed thereonand the flexible membrane after it is rolled up as a neural probe. FIG.9C shows a 120 μm diameter polyimide membrane suitable for a neuralprobe. FIG. 9D shows a 350 μm diameter polyimide membrane suitable for aneural probe.

FIG. 10 is an image of a 3D coil which is suitable for use as a neuralstimulator. Out-of-plane 3D coil structures place the coil axisparallel, rather than perpendicular, to the substrate plane. The 3Dcoils can be formed from materials that have a built-in stress profile.The stress profile can designed into a thin film by varying the growthconditions appropriately during deposition to produce coil structureswhich include released elastic members that bend back on themselves andcontact the substrate producing loop windings of the coil. Preferablythe elastic member is formed of a conductive material. Alternatively,one or more layers of conductive metal, such as gold, copper or silver,may be formed on an inner surface, an outer surface, or both surfaces ofa non-conductive layer. By using or adding one or more conductivelayers, a coil structure suitable for use as a neural stimulator can bemanufactured. Further details regarding 3D coil structures and methodsof making 3D coils structures are described in U.S. Pat. Nos. 6,392,525,6,534,249, and 6,856,225 which are incorporated herein by reference.

An out-of-plane coil structure comprises a substrate with elasticmembers, each elastic member having at least one anchor portion fixed tothe substrate and an elastic portion that, when released from thesubstrate, forms a full or half loop of the 3D coil. The elastic portionis initially attached to the substrate, but after it is released fromthe substrate curves to form at least a portion of a coil loop due tothe stress profile in the elastic member. Out-of-plane coils as shown inFIG. 10 are formed by closing half loop pairs of elastic members. Uponrelease of the released portion of the elastic member, the half looppairs need only to be coarsely aligned to each other and connectedtogether, such as by either plating or soldering. The loop halves neednot be the same length. One side could be longer than the other tofacilitate the overlap. A different release material may be used undereach loop half to release the loop halves sequentially.

According to some embodiments, the elastic members may form the wholeloop and may include a second anchor portion that is connected to thesubstrate as described in more detail below. The second anchor portionand the loop winding are initially fixed to the substrate, but arereleased from the substrate to become separated from the substrate. Anintrinsic stress profile in the elastic member biases the second anchorportion away from the substrate forming the loop winding and causing thesecond anchor portion to contact the substrate. The resulting coilstructure is out-of-the plane of the substrate. The loop winding mayalso include a plurality of turns.

Various techniques may be used to position the second anchor portionaway from the takeoff point of the elastic member, either tangentiallyor axially. If the second anchor point is positioned tangentially fromthe takeoff point, the loop winding is generally in the shape of adistorted circle, i.e., the second anchor portion contacts the substratein the same vertical plane as the first anchor portion. Varioustechniques may be used to position the second anchor portiontangentially from the takeoff point. For example, a mechanical stop canbe fixed to the substrate at the desired location to catch the secondanchor point while it is detached from the substrate. Also, the radiusof curvature of the elastic member may be varied, such as by adding aload layer onto a portion of the elastic member or by patterning one ormore openings or perforations into a portion of the elastic member.Various techniques can be used to connect the second anchor portion tothe substrate. For example, the second anchor portion can be soldered orplated to the substrate. Each anchor portion can be attached to a metalcontact pad attached to the substrate, for providing electricalconnectivity to other elements in a circuit.

One difficulty in creating out-of-plane structures is ensuring that theelastic members used to form the loops are not bunched or entangled byhydrodynamic and surface tension forces when they are being released. Ithas been observed that aqueous release and drying of the releasedelastic members causes insufficiently stiff fingers to get pulled aroundby the air liquid interface and stick together. The longer and narrowerthe released elastic members the greater is the problem. A relateddefect occurs when released elastic members intertwine. Anotherdifficulty is providing enough contact area for the free end of thereleased elastic member where it makes mechanical contact for subsequentelectroforming. A further difficulty is calibrating and maintaining thestress parameters in the metal deposition process in order to keep thediameter of the coil, and as such its inductance, within a few percenttolerance.

FIGS. 11 through 15 illustrate methods of making the 3D coil structuresfor neural stimulation. Referring to FIGS. 11 and 13, a release layer 10such as Ti, Si, or SiN is patterned on membrane 20. The membrane may beany material that is flexible and suitable for rolling or folding into aneural probe. The release layer 10 may be a material that can be quicklyremoved by selective dry or wet undercut etching. Possible etchants fora Si release layer include KOH (wet processing) and XeF.sub.2 (dryprocessing). Hydrofluoric acid will etch Ti or SiN release layers.

A layer of an elastic material is deposited on substrate 20 andpatterned into four individual elastic members or fingers 18. Eachfinger 18 can be formed of a single elastic material 23, such as astress graded film of NiZr, Mo/Cr, solder-wettable Ni, or other suitablematerial. Alternatively, each finger 18 can be formed of two or threelayers: a bottom gold layer 24, for example, can be used to form theouter skin of the coil when released and provides a high conductivitypath for electrons at high frequencies. A second gold layer (not shown)can be deposited on top of layer 23 to passivate the surface. The addedlayers may also serve as a seed layer for subsequent plating. Dependingon the design required, any metals capable of holding large stresses maybe used to form the parts of the finger that induce bending, and cladthem with additional layers that are good seed layers for plating.Alternately, the stresses may be placed into a material that containsthe required bending moment and is also suitable for plating orsoldering, for example Ni or its solution hardened alloys.

Referring to FIG. 11, two cross tethers 14 were deposited and patternedto connect or join at least from one released elastic member 18 in thearray of four fingers 18 to one additional released elastic member 18 inthe array. Tethers 14 are shown as substantially perpendicular to thelength of members 18, but may be disposed diagonally or some otherconvenient orientation for maintaining the spaced-apart separation ofthe released elastic members. The release mask 17 allows a release etchto undercut both the released elastic members 18 and the tether 14.Although two tethers 14 are shown in FIGS. 11 and 13, only one may beused or more than two may be used. The tether 14 may be perforated withone or more perforations 12 to allow release etchant to pass through thetether layer 14 through an aligned hole 12 in the elastic member layer18 in order to more rapidly release the finger 18. In FIG. 11, a tetherlayer 14 is placed near the four tips 11; a second tether layer 14 isplaced near the center of the fingers 18. FIG. 16 shows the releasedcoils formed into connected coils 18 with tether layers 14 still inplace.

The tether layers minimize or eliminate the floppiness problem of verylong flexible released elastic members (the longer the released elasticmembers, generally the greater the problem). Longer, thinner releasedelastic members also have a tendency to intertwine after release. Byplacing cross-tethers on the elastic members that release along with theelastic members, this problem is also eliminated. The tethers are madenarrow enough to ensure that release etch releases them along with theelastic members. The tethers maintain uniform released elastic memberelement array spacing and prevent the released elastic members fromtouching or entangling after release and when the tips are beingconnected to their respective pads. The ensemble of tethered releasedelastic members behaves like an effectively stiffer structure. Thetether material should be non-conducting in order to provide electricalisolation of electrically conductive released elastic members.

The out-of-plane coil structures are particularly beneficial when usedas inductors or transformers in integrated circuits. While theindividual released elastic members may be formed of a metal stressgraded material, or multi-layers of metal and stress graded material, inmany applications, the structure will be plated with metal in a platingbath after the released elastic members are released and the free endsconnected to the contact pads. As described below, resist reflow is usedto protect certain areas of the structure from the plating bath. Thereflow step could also be used to reflow the tethering material,particularly if the tether material is the same as the reflow material.If the amount of reflow is too large, the tethers could neck down andeven separate into drops of resist on each finger. To avoid this, aseparate mask can be used to define the tether layer, or the tetherlayer can be combined with the load layer (if a load layer is added tothe structure—as described below) into a single layer separate from therelease layer. If, for example, the release layer is made of resist, thetether-load layer could be made of polyimide. Reflow of the resist wouldnot reflow the polyimide, because of the wide separation of their glasstransition temperatures.

When a separate tether-load layer material is used, when the releasewindow 16 is removed the exposed release metal that was used as a commoncathode can be cleared away. The tethers may remain in place for thisand subsequent dicing and packaging steps because although the platingstep stiffens the released elastic members, once the tethers areremoved, individual released elastic member loops may bend into adjacentloops. The tethers can and will typically be removed afterelectroforming. However, there may be some applications where it will beappropriate to leave the tethers in place.

If the tethers are combined into the release window mask, no added maskcount is needed to implement the tether layer, making it effectivelyzero cost. The tethers proposed can be implemented in the release windowmaterial that in the process flow serves to define where the releasedelastic members lift and also where the electroplating occurs. If thetethers are not combined with the release mask, then a three maskprocess may be needed, which is still possible to implement at low cost.

The rate of Ti release layer undercut below both released elastic membermetal and photoresist has been characterized. The undercut rate in therelease etch under both released elastic member and tether materials isidentical and rapid. Release times for released elastic members with 200nm Ti is on the order of 0.34 microns/sec, meaning that 50 micron widereleased elastic members take about 74 seconds to release. Tethersnarrower than 50 microns will release during the same process. Muchnarrower tethers may be used, on the order of 20 microns; these tetherswill interfere even less with the release process. Tethering effectivelyreduces the length-over-width ratio of the released elastic membersegment. The inventors have demonstrated that 100% yield withoutbunching or tangling is routine if length/width limits are not exceeded.

After release and coil closure, the tethers are located on the inside ofthe coil. At high frequencies, currents flow on the outside of the coil(made of an electrically conductive material) due to the skin effect. Toavoid shorting between adjacent coils formed of an electricallyconductive material, the tether material should be made of anon-conductive material. No plating will occur where an insulatingtether resides, however this will have no significant electrical effecton the final device.

In accordance with another embodiment, a graded density of perforations12 disposed along the length of the spring 18 may be used to control therate of release of the released elastic members 18. FIGS. 11 and 13 showone way in which a graded perforation density may appear in the layoutof a coiled spring array. Note that the spacing between perforations 12is increased gradually from the tip 11 to the base of the releasedelastic member 18. Note also that, if a load layer 13 (described below)is also present, perforations 12 in the loaded section 13 of the beam 18go through both the load layer and elastic member layers 23 and 24.

The graded perforation density in elastic members 18 enables the releasefrom the substrate to be in a controlled fashion starting with the tip11, and progressing toward the base. This is important because of thelarge amount of elastic energy that is stored in the elastic memberbefore release. If the release rate of the energy is too rapid, theelastic member can reach enough speed to entangle with other elasticmembers or break. Gradual release of the elastic member allowsmechanical damping enough time to limit the total kinetic energy of thespring to a non-destructive level.

Perforations may also be used to create varied inductance values fromone individual coil to another or from a series of coils to another.Typically, for a given thin film deposition sequence, only one coil areais created. This happens because typically only one main radius iscreated, and if a load layer is used, one loaded radius. To obtaindifferent inductance values, the number and pitch of the windings mustbe varied. The number of windings can only be varied discretely, hence,the pitch must be used to fine tune inductance values for a given looparea. If a design calls for more than one inductance, then there will bevaried finger widths. To ensure that the fingers all release atapproximately the same time, with the same release layer undercut, theuse of graded density perforations, with the same approximate densitiesis required. The graded perforation density can be used to ensure thatall elastic members release at the same rate, regardless of width.

Tethers may be used in addition to the graded perforation density. Insome cases, it may be possible to locate the tether layers in betweenperforations. In other cases however, if the tether must pass over aperforation, that area of the tether must be either removed orperforated so that the release etch is not blocked. If a load layer ispresent, the perforation should pass through the load layer so thatrelease etch is not blocked. Any structure pertaining to the load layerthat is present during elastic member release must not block the releaseetch from passing through the elastic member perforations. Thistypically calls for making perforations in both the spring definitionmask and in the load layer definition mask in order to define anoperational perforation 12.

Load layers have been used to vary the radius of curvature of theelastic member. The load layer 13 is an additional layer patterned onthe elastic member 18 to apply stress that either increases or decreasesthe bending radius. The load layer 13 is patterned to reside generallyin the middle segment of the elastic member 18. The load layer istypically made of metal, such as gold, Mo, MoCr alloy, Ni, Ni alloy etc.

A load layer 13 made of a reflow material such as photoresist can beadvantageously used to load elastic members 18 to increase the radius incomparison to the same beam without the resist. The resist can beintroduced in the same masking step that creates the release window, orit can be introduced in a separate step. The resist has very lowintrinsic stress when it is processed. Once the spring is released, theresist is typically on the inside of the bending cantilever, andtherefore it accumulates compressive stress as it opposes the bending.One desirable feature of the resist is that the loading effect of theresist can be gradually changed with either heat or plasma ashing. Heatpermits the resist to soften, and above its glass transitiontemperature, to flow. For Shipley 1813 resist, it was observed that theloading effect was substantially reduced at 185 C, and was furtherreduced at 200 C. The loading effect can be substantial. In oneexperiment, the inventors altered the released elastic member diameterfrom 495 down to 345 microns.

Plasma ashing of the photoresist load layer 13 is another way to controlthe released elastic member diameter. Ashing permits gradual controlledreduction of the resist thickness without attacking the spring metal. Asthe resist thickness is reduced, the diameter shrinks.

The resist defining the release window will typically be reflowed inorder to seal off the edge of the release metal to block plating alongthe edge of the window. This reflow step may relax some or all of theload created by the loading resist. If desired, the load layer resistand the release window resist can be two separate materials withdifferent glass transition temperatures.

Using a load layer formed of a reflow material such as resist, increasesthe stiffness and radius of the released elastic members while they arestill in the release etch. Once the released elastic members are removedand dried, the reflow step tightens the radii. This can be performed inair, where there is reduced likelihood of sticking or entangling. Thetrajectory of the free end of each cantilever is therefore determined bya two step process of first releasing the elastic member and thenreflowing a reflow load on the released elastic member. This two steptrajectory is preferred because the step of placing the tip to itstarget contact point can be done slowly and in air in the absence ofsurface tension forces.

A load layer of sputtered material, preferably metal can be introducedto produce a loaded section of an acircular beam. The loading effect ofthe metal can be controlled by selecting the layer thickness, intrinsicstress and modulus. Since it is desirable to keep the layers thin inorder to minimize etch times and undercut, utilization of non-zerostress to minimize the amount of metal needed may be advantageous. For agiven material, the elastic modulus is fixed, however, the stress may becontrolled to minimize the required thickness. For example, acompressive load applied to the inside surface of a beading beam willexpand the radius of the beam more than a neutral or tensile load.

The width of the load layer can be varied in order to adjust the amountof change induced in the released elastic member. For example, byapplying a load layer that exactly balances the bending moment of thereleased elastic member when its width equals that of the releasedelastic member, the radius of the loaded elastic member can be variedfrom infinity down to the released elastic member's natural radius byvarying the width of the load layer. Different springs, or differentsegments within released elastic members can have different radiiwithout introducing more than one load layer by simply altering the loadlayer width.

To control the thickness of the load layer and the resulting stress, theload layer may be a multilayer. The layers that comprise the releasedcantilever can include a bottom layer of seed metal for plating, thelayers of stressed spring metal, a top layer of seed metal, a layer ofload metal, and additional seed metal in case plating is desired on theloaded segment. The load layer may be fabricated from the same materialas the spring metal. This simplifies the processing. All of the layerscan be deposited in the same deposition apparatus by sequentialdeposition.

Gold can be used as the seed metal for plating. The seed metal will havesome loading effect of its own. It is possible therefore to load thebeam with the multiple layers of seed metal. Gold is soft however, andhas a smaller modulus and yield stress than the metals typically usedfor the springs. More efficient loading can be achieved with springmetals such as MoCr. Ni and Cu are also possible seed metals forplating, and may have a cost advantage over gold.

One configuration for making a multi-turn coil out of a series ofindividual coils is to pattern the base of the elastic member in theshape of an inverted “Y” or “U”. Referring to FIG. 22, elastic members18 include inverted base pads 118 (in the shape of a “U”). The contactpad 119 for an adjacent coil can then be positioned within the spaceprovided by the “Y” or “U” configuration of base pad 118. One way toincrease the yield of the Y-spot loop (as described in the '815application) is to extend a narrow tip 11 on the elastic member 18 toallow this tip 11 to bisect an extended portion 120 of the Y past thecontact pad 119. This permits coil completion without shorting, even ifthe radius is tighter than required to stop the free end 11 at thecontact pad 119. It is worth noting that since the inductance isproportional to the loop area which varies quadratically with radius,the percentage error in inductance is twice the percentage error inradius.

This sensitivity to radius error is of concern for several reasons.First, process nonuniformity within the sputter tool will produce somevariation in the radius within a wafer and from wafer to wafer. Furthervariations can occur from run to run. It is highly desired to reduce thesensitivity of the loop area to process variations that cause the actualradius to deviate from the design radius. One way to achieve this is tocause the free end to hit a mechanical stop of some kind. This forcesthe coil area to depend on physical layout variables rather than processvariables. The mechanical stop can take a variety of forms, and provideseveral levels of constraint.

One simple constraint illustration is provided by the acircular loadedbeam. By simply loading a forward segment of the finger 18 (such as bydepositing a load layer 13 to a smaller length than shown in FIG. 1),the tip 11 is forced to hit the substrate rather than wrapping insidethe coil. The substrate provides a degree of mechanical constraint onthe tip 11 since the tip 11 cannot penetrate the substrate. The free endtip 11 can still slide on the surface. To constrain the tip 11 further,a raised stop 25 on the surface of the landing pad can be introduced toprevent the free end from sliding closer than a given distance towardsthe takeoff point. Further, lateral raised stops 26, 27 (FIG. 12) can beplaced to either side of the landing pad to guide the tip 11 and toprevent it from sliding to either side. The edges of the lateral stops26, 27 can further be tapered in a horn like structure to gather thefree end 11 of the finger 18 and funnel it into its desired location.The mechanical stops should not block the entire cross section of thepad available for plating, since this might create a segment of highresistance in the coil. To produce a stop, it is only necessary for thestop to touch a portion of the free end 11 in order to constrain itsmovement. Tip 11 is shown as tapered to facilitate positioning and finalconnection to the contact pad.

The stop can be formed from a released elastic member. If formed from areleased elastic member, no additional masks are needed to make thestop. A loop formed by such a structure will have a long elastic memberand a short elastic member or tab. The long and short elastic memberscan interlock with each other to constrain their positions.Additionally, the design can provide for the long elastic membertouching both the short elastic member and the substrate if desired.Design constraints may be included in the coil such that errors in thefully relaxed radii of the segments do not produce proportionate errorsin the coil cross-section. Structures that close until they hit a stopand then stop without fully relaxing have this desired property.

In addition to or in place of a mechanical stop, a tacking operationthat adheres the tip 11 in its desired location prior to plating is auseful structure for improving device yield. By tacking the tip 11 inplace, it is less likely that the electroplating bath can move the tip11 before the electroforming operation solidly anchors the tip 11. Thetacking can be achieved for example by melting and flowing a smallamount of material between the tip and pad, and then hardening it. Thiswould be the natural outcome of designing in a small amount of releasewindow material at the contact point. The reflow operation describedabove will also tack the tip in place. This can therefore be implementedwith no change in cost. The tacking area is intentionally kept small tominimize the contact resistance. The tethers further serve to ensurethat the tips that are not fully tacked remain in proximity to the pad.FIG. 11 item 19 shows a strip of release window material that could beused to tack the tip 11 in place.

It is highly desirable to be able to tune the radius of the elasticmember 18 after release, especially if the sputter process produces aradius that is not the desired radius. This can be achieved bysurrounding the elastic member 18 with additional layers of metal thatcan be selectively etched away to alter the load on the released elasticmember. Each time a layer is removed, the released elastic member willbend by a small amount, allowing the radius to be tuned. When the radiusis tuned correctly, the processing can then continue onto theelectroforming step. By making the layers thin and/or properly adjustingtheir stress, the amounts of radius change can be kept small, on theorder of a few percent.

No added mask count is needed to implement radius tuning, because theselective nature of the etch defines the start and stop points of thelayer removal. Further, no additional materials are needed, since themultilayers utilized can for example consist of the spring and seedmetals (e.g. MoCr and Au) already used.

To make radius tuning compatible with plating, it must be ensured thatafter the radius is tuned, the surface exposes metal that can be plated.In the current industry practice, this means making bilayers of Au andMoCr, and etching down to the next layer of Au.

An alternate method of forming an out-of-plane coil structure in whichtwo half loops are closed in mid-air forming a loop winding is shown inFIGS. 14 and 15. The elastic layer is photolithographically patternedinto a series of individual elastic members. Each individual elasticmember includes a first elastic member 31, a contact portion or bridgefor connecting between adjacent loop windings 35 and a second elasticmember 32. First elastic member 31 includes an end portion 33 in theshape of an elongated tip and second elastic member 32 includes an endportion 34 having a groove for receiving elongated tip 33. Thisstructure of tips 33 and 34 facilitates catching of the two springsafter release so that the two portions may be connected via soldering orplating. The loop winding is formed by removing the release window undereach first elastic member and each second elastic member. This can bedone at the same time, or sequentially, by using a release materialunder all the first elastic members different from under all the secondelastic members. The first and second elastic members can also bereleased at different times by placing different perforation densitieson them. This causes tip 33 to move in the direction of arrow 38 and tip34 to move in the direction of arrow 39. When the two tips meet, theyare joined at point 40. Pressing and heating causes the solder to reflowand join free end 33 to free end 34.

The elongated tips 33 may be, for example shaped as shown in FIG. 17 orFIG. 18. In addition to the shape shown in FIG. 15, end portion 34 maybe of the shape shown in FIG. 18. Other variations are possible.

Alternatively, the free ends (without solder) can be connected togetherby plating. Immersion in a plating bath and depositing metal onaccessible metal surfaces both thickens all metal lines and createsbridges between proximal surfaces.

The individual loop halves are shown in FIGS. 14 and 15 as being ofapproximately the same length. However, the lengths can be varied to aidin the coil formation process. For example, the first elastic memberscan be made shorter than the second elastic members to ensure that thesecond elastic members overlap the first elastic members.

An alternative layout for a series of elastic members to be released toform a closed loop structure is shown in FIG. 19. In this embodiment,each elastic member 1930 is patterned into two segments. The firstsegment 1931 extends from anchor portion 1934 until it reaches secondsegment 1932. Second segment 1932 is patterned at an angle from firstsegment 1931 and is terminated by tip portion 1933. A plurality oftethers 14 are added to maintain the spacing between the elastic members1930. When the release layer is removed, tip 1933 is released followedby second segment 1932 and then segment 1931. When tip 1933 contactscontact 1934 of the adjacent member, the resulting loop is notacircular. The mid-air jog, which occurs where the first and secondsegments join 1935, allows the free end 1933 to return to the take-offpoint with an axial offset.

The resistance of the loop closure may be reduced by connecting the freeend of a loop back to a contact pad on the substrate with lowresistance. Obtaining low resistance at the contact pad requires a goodmetallurgical junction consisting of highly conducting materials. Coilstructures incorporating a solder pad that is reflowed to close the loopachieves a good metallurgical junction as well as low contactresistance. Alternatively, the free end may be joined to the contact padby plating, either electroless or electroplating. In this method, theloop is formed by releasing the elastic member. The free end comes intoeither mechanical contact or proximity to a contact pad on the inductorsubstrate. Then, plating applies conducting material around both thefree end and the contact pad, forming a continuous joint between them.In this embodiment, the application of material need not be limited tothe free and the pad areas only. Preferably, the plated material hashigh conductivity, and is plated throughout the loop in order to reducethe coil resistance, thereby beneficially increasing the quality factor.

It is desired from a reliability standpoint to have as wide a pad areaas possible in order to accommodate possible axial offsets of the springends with respect to their bases. This offset could for example becaused by helical bending due to stress anisotropies, or due todisplacement of the fingers due to surface tension forces during wetprocessing.

One possible way to extend the pad area is to release elastic membersfrom opposite directions. This also enables the released elastic membersto be made wider. FIGS. 20 (before release) and 21 (after release) showa schematic of the layout. In FIG. 20, elastic members 81 and 82 arelaid out to release from the left to the right. Elastic members 83 and84 are laid out to release from right to left. Oversized contact pads71, 72, 73, 74, 75 and 76 are also shown. This design is advantageous ifthe undercut can be minimized. A problem may arise in that the releasewindow that opens to allow the springs to lift, will also allow therelease etch to advance toward the adjacent pad. Normally, the undercutetch of the release layer is about 30% larger than the undercut neededto release the springs. So, if the undercut needed is 20 microns, theundercut allowed for is about 25 microns. This may be too large in somecases.

A solution to the undercut problem is to clear the conducting releaselayer between the spring metal traces before applying the releasewindow. This has the drawback that the release layer then cannot be aseasily used as a common cathode for electroplating. The technique maywork for electroless plating, however the conductance of electrolessplated metals is typically lower than what is achievable withelectroplating. Conductance has to be kept extremely high in order tomeet the quality factor requirements of some applications.

Making the elastic members release from two sides and interleave doesnot permit the use of tethers since tethers would prevent interleaving.Without tethers, some stiffness and spacing rules may need to be mademore conservative in order to prevent entanglement or shorting. Densetoroids designed to lift with their spring tips to the outside andlanding pads to the center would not likely be a useful application ofthe bidirectional springs.

The method of the invention permits process extensions. These processflows are exemplary, but other variations are possible. For example,certain process steps described herein may be combined or eliminated.Layers of solder used to close the loop, could also serve as the releasewindow for the spring release step.

Neural stimulation techniques discussed herein are directed tohigh-precision spatial targeting of nerve circuits by shaping magneticfields. The neuromodulation devices disclosed herein provideminimally-invasive and/or feedback-controlled neural modulation forregulating brain stimulation, in particular the visual cortex. Thefocused magnetic stimulation (FMS) neuromodulation approaches disclosedherein are underpinned by metamaterial coils as discussed above. Thesemicro-engineered metamaterial structures allow for far greater controlof electromagnetic fields over conventional transducer technologies.Driven by smart current distribution algorithms, FMS can providetailored stimulus patterns. The use of an array of metamaterial coils asdescribed above combined with a current distribution algorithm enablescomplex stimulation patterns.

The use of magnetic stimulation using an array of micro-coils asdescribed herein facilitates safely and selectively writing to neuronsin the visual cortex. Embodiments disclosed herein use focused magneticstimulation (FMS), an electromagnetic field manipulation scheme thatgoes beyond traditional magnetic stimulation, to provide previouslyunachievable scale, precision, and in vivo adaptability. Using FMS,multiple neurons can be targeted by magnetic beam scanning, beamsteering, and beam focusing.

The use of flexible electronics, underpinned by TFT circuitry reducesthe amount of inflammation and glial scarring when implanted. Theflexible platform also accounts for brain motion. The TFTs can enablelogic circuits, multiplexers and shift registers, designed toindividually address transducers (sensors and/or stimulators) locally,thereby significantly reducing the number of data lines that need to berouted upstream to the low-power internal electronics module.

FIG. 23 shows a probe 2340 supporting an array of stimulationmicro-coils 2342 interweaved with an array of neural sensors 2341. Thedense pattern of coils 2342 on and/or within the shaft of the probes2340 can be used to stimulate nearby neurons. Interference effects canbe used to steer the field to some degree, but localization away fromthe immediate vicinity of the probe may be somewhat limited. The corecontrol module ((CCM) 521 shown in FIG. 5) can be configured to controlone or more parameters of the current pulses applied to the micro-coils2342 through the neural stimulation bus 545 a, including at leastamplitude and phase of the current pulses. The current pulses to thecoils 2342 may be controlled so the electromagnetic fields produced bythe coils 2342 undergo constructive and destructive interference thatfocuses and/or steers a magnetic flux density to one or more neurons2301 of interest. The constructive and destructive interference isconfigured to confine the magnetic flux density produced by the coils2342 to a focus area 2305 or region of interest within the visualcortex. The focused magnetic flux density causes the one or more neuronsof interest 2301 a to be activated and causes minimal activation ofother neurons 2301 b that are outside the focus area 2305. In someimplementations, in addition to the control of the amplitude and phaseof the current pulses, the CCM 521 may be configured to control otherparameters of the current pulses such as the duty cycle and/or frequencyof the current pulses that drive the micro-coils 2342. For example, thecurrent through the coils may be between about 30 to about 70 μA, e.g.,about 50 μA. The duration of the current pulse may be about 100 to about200 μs in some embodiments.

Time-varying electrical currents through the micro-coils generatemagnetic fields, which in turn will induce electric fields (Faraday'sLaw). Like electric stimulation, the induced electric field from thecoil will modulate the membrane voltages of nearby neurons, and ifstrong enough, will lead to their activation (i.e., the generation ofaction potentials). Magnetic stimulation offers significant enhancementsover the state-of-the-art electric stimulation, including but notlimited to the following:

(1) the electric fields from magnetic stimulation are highly asymmetric,unlike the electric fields arising from electrodes. This spatialasymmetry is very important because it can be exploited to selectivelyactivate desired neurons, while leaving others quiescent.

(2) The stimulating efficacy of the micro-coils remains constant overtime. This is due at least in part to the fact that magnetic fields passreadily through biological substances, and therefore coils remainfunctional even if they become severely encapsulated due to biologicalresponses to foreign bodies.

(3) There need not be any direct contact between the metal coil andneural tissue, and thus, direct electric currents do not flow into thebrain.

Magnetic stimulation by micro-coils is safer and reduces many of theproblems that occur at the interface between a stimulating electrode andthe brain. In order to keep the neural implant power budget withinspecified thermal safety limits, it can be helpful to operate the coilsat the lowest current possible. In some embodiments, e.g., the visionapplication described herein, it may be useful to predominantly activateneurons in a single orientation while minimally activating neurons inother orientations or not activating neurons in other orientations.

The 3D coils can be configured to satisfy the low current operation,precision and selectivity. Three dimensional micro-coils, such as thosedescribed herein, can be configured to yield an order of magnitudelarger electric field gradients (the metric for neuron activation) thantheir planar coil counterparts having similar areal dimensions. FIG. 24Ais a graph showing the electric field gradient (log plot) of 3D coilsvs. an equivalent planar coil. FIG. 24B is a graph showing thepenetration depth for a 3D coil as a function of current. The magnitudeof the electric field gradients produced by the 3D micro-coils allowoperation of the micro-coils down to about 50 μA as compared tomilliamps of current required for planar coils of similar arealdimensions. For example, in some embodiments, the use of the 3Dmicro-coils in place of planar coils having similar areal dimensions asthe 3D micro-coils can reduce the total dissipated power of 100 k coilsby about 100 times, e.g., from several Watts to several 10's ofmilliwatts. As shown in FIG. 24A, for operation at small current, e.g.,down to about 50 μA, only the 3D coil is above the activation threshold(1100 V/m²) for neurons. Three dimensional coils have been mass-producedon prefabricated wafers prior to dicing, bonding and packaging. They canalso be fabricated on flexible substrates, the approach used for thevisual prosthetic system described herein. The resolution of the coilsis dependent on their overall dimensions. In some embodiments, thediameter and/or length of the micro-coils may be less than 20 μm whichis less than the size of a cortical neuron. Furthermore, unlike planarcoils, there are more degrees of freedom to control the direction ofstimulation. In 3D coils, the depth of penetration in the tissue isproportional to the size of the coil, but for a fixed coil size, itdepends on the magnitude of the injection current as shown in FIG. 24B.

Additionally far greater control over the fields generated by themicro-coils 2342 can be realized using a focused magnetic stimulation(FMS) scheme. In FMS, the magnetic fields are dynamically shaped byusing an array of three-dimensional micron scale coils 2342, driven byphase and amplitude-controlled currents. This results in constructiveand destructive interference of magnetic fields. Driven by tailoredcurrent injections in the coils, FMS enables more localized stimulationin between coils (enhanced focusing), better depth control, and complexstimulation patterns (beamshaping and beamsteering), as compared tocurrent stimulation methods. Tailored stimulations can be obtained withappropriate coil array designs, by selecting the optimal number ofelements, array configuration, driving circuits, and currentdistribution in the coils 2342. Focusing the coils can be achieved byvarying drive currents in each coil. Electronic steering can be achievedby modifying the intensity of the currents in each coil 2342 usingindependent driving circuits.

In some embodiments, the magnetic flux density within the focus region2305 is greater than about 0.1 Tesla, the electric field strength withinthe focus region 2305 may be about Ex=dV/dx>100 V/m, an electric fieldgradient within the focus region 2305 may be about dEx/dx>500 V/m²and/or a maximum electric current pulse amplitude in each coil may beless than about 500 mA or even less than about 100 mA. In someimplementations, the magnetic flux density, electric field strengthand/or electric field gradient produced by the micro-coils 2342 issufficient to activate one or more neurons 2301 a within the focusregion 2305.

Referring again to FIG. 23, a dense pattern of sensing electrodes 2341on and/or within the shaft of the probe 2340 can be used to stimulatenearby neurons. Sensing neurons is performed using an array of neuralsensors. The neural sensors are interspersed with the neural stimulationcoils as shown in FIG. 23. As the action potentials of neurons producelarge transmembrane potentials in the vicinity of their somata, theseoutput signals can be measured as a voltage difference by placing sensorelectrodes in close proximity to the neurons. To be able to localizesingle neurons, sensors comprise a compact electrode array (CEA) ortetrodes. A tetrode has four electrically isolated electrodes and theposition of the sensed neurons can be estimated by triangulation of thesignals picked up by the four electrodes of the tetrode. Triangulationof the signals to determine the neuron position relies on the fact thataction potential amplitudes decline as a function of distance betweenthe electrode tip and the neuron. The advantage of using tetrodes,beyond localization, is that they allow a significant reduction in thenumber of monitoring elements. For example, one tetrode can record about1000 neurons, within a 300 μm diameter. In order to carry the signals ofa large number of sensors over the flexible membrane to the ADC, thesensor signals of the electrical transducers are multiplexed into onesignal over a shared data line.

The CCM 521 provides signals to the front end electronics 543 a b, c forselection of the column and row of the selected micro-coils 2342 of theprobe 2340 through the neural stimulation bus and the neural stimulationcontrol bus.

FIG. 25A is a diagram illustrating row and column addressing through theneural stimulation bus and the neural stimulation control bus for theelements of an micro coil array 2500 C11 through CRC. Each elementC11-CRC includes a coil and driver circuitry as shown in FIG. 25B. Eacharray element C11-CRC is selected by the neural stimulation bus thatincludes lines D1 through DR and neural stimulation control bus thatincludes lines G1 through GC. A similar row and column addressingstructure can be used for the neural sensors.

Through the neural stimulation bus and the neural stimulation controlbus, the CCM 521 provides a predetermined voltage for a coil drivercircuitry 2525 shown in FIG. 25B. The value of Dn determines theamplitude of the current pulse(s) delivered to the coil associated withthe coil driver circuitry 2525. The timing of the application of Vss andVcc to a coil driver circuitry 2525 by the CCM 521 determines the phase,duty cycle, and/or frequency of the current pulses provided by thedriver circuitry 2525 to the coil 2542.

To program a particular coil 2542, Vcc and Vss are set to zero. Aparticular column of the micro-coil array is activated by applying avoltage to Gn and a value Dn is applied to the transistor 2527 to setthe pulse amplitude value in the gate capacitors 2526 for the coil 2542.The proper bias voltage is set on Dn for the appropriate amount ofcurrent that the coil requires, which may be positive or negative.

To activate the coil 2542, Gn and Dn are disabled and Vss and Vcc areapplied to the driver circuit 2525 for a duration commensurate with thestimulation parameters. Bipolar operation is enabled by connecting thepair of capacitors 2526 to the complementary pair of transistors 2528.

The current pulse through the coil 2542 generates a magnetic field.Referring now to FIG. 26A, which shows a single loop coil, and Equation(1), the magnetic field created by each loop, H_(z) ^(LOOP), increaseswith the radius of the loop, R, and the intensity of the current, i(t),and decreases with the distance, z, along the axis.

$\begin{matrix}{{H_{z}^{LOOP}(z)} = \frac{\frac{1}{2}R^{2}{i(t)}}{\left( {R^{2} + z^{2}} \right)^{1/2}}} & (1)\end{matrix}$

The magnetic field of a coil depends on the number of turns, N, thelength, l, the pitch, α, and the amplitude of the current as indicatedby FIG. 26A, which shows a small radius coil, and Equation (2). Byincreasing N (or the inductance of the coils), and 1, we canconsiderably increase the resulting magnetic field even for a fixed lowcurrent and small radius coil, as deduced from Equation (1). Thus,arranging a large number of small coils in an array configuration, asshown in FIG. 26B will yield an increase in the magnetic field intensityand penetration to specific regions.

$\begin{matrix}{{H_{z}^{COIL}(z)} - {\frac{i(t)}{4\pi\; r\;\tan\;\alpha}\left\{ {\frac{{N\;\pi\; r\;\tan\;\alpha} + z}{\sqrt{r^{2}} + \left( {{N\;\pi\;\tan\;\alpha} + z} \right)^{2}} + \frac{{N\;\pi\; r\;\tan\;\alpha} - z}{\sqrt{r^{2}} + \sqrt{r^{2}} + \left( {{N\;\pi\; r\;\tan\;\alpha} - z} \right)^{2}}} \right\}}} & (2)\end{matrix}$

FIG. 27 is a schematic representation of beam focusing and beam steeringwithin a focus region. As illustrated in FIG. 27, since each coil 2742is driven by a coil current that is independent of other coil currents,it is possible to manipulate the field strength of the electric field ata selected location, such as the focal point 2705 a within focus region2705, by approximately adding the linear vectors 2765 of the individualfields. Thus, tailored stimulations can be obtained with appropriatecoil array designs, by selecting the optimal number of elements, arrayconfiguration, driving circuits, and current distribution in the coils.

Embodiments disclosed herein use a suite of algorithms for parallel dataprocessing to convert image signals from the camera into coilstimulation signals. The algorithm suite as illustrated in FIG. 28Aprovides a general neural interface platform that supports thetherapeutic vision prosthetic system.

(1) To enhance accuracy and reduce bandwidth and computation duringon-line operation, an offline, off-board array calibration procedure maybe employed. The calibration procedure involves determining which neuralsignal spikes are caused by a particular neuron. The calibrationprocedure acquires a model by sequentially sampling small neighborhoodsof the patient's cortex at high sampling rates (22 kHz) to identify thenumber, location, type, orientation, firing rate and amplitudedistributions of neurons.

(2) The calibration procedure (1) enables an online, on-board signalprocessing algorithm to perform spike sorting. The information obtainedby the calibration procedure is used by the signal processing module togenerate coil pulse configuration patterns to stimulate neurons withknown registration to those neurons read by spike sorting.

(3) A second offline, off-board procedure infers the circuit structureof the cortex. Circuit inference provides key parameters such aselectrode depth relative to cortex surface. Circuit inference may beused on intact animal models to infer relevant features. Algorithms toestimate retinotopic mapping and feature distribution that exploitpattern matching and information theoretic methods can be used.

(4) The information obtained by the circuit inference (2) and thecalibration procedure (1) and signal processing (2) is used by theon-line, on-board neural coding algorithm. The neural coding algorithmtranslates visival stimuli (from the camera) into activation patterns todrive the coil currents in the signal processing layer (2).

(5) The vision prosthetic system includes a user interface that allowstherapists to configure the system, monitor performance parameters, andinitiate off-board communication to allow calibration and circuitinference.

(6) Authentication, compression and encryption services connect thevarious modules in the prosthetic system across hardware boundaries.

(7) A simulator can be used to evaluate algorithm design choices,optimize algorithms, and/or provide unit testing.

FIG. 28B is a diagram that illustrates methods implemented by the visionprosthetic system to provide neural stimulation so as to simulate visionin a visually impaired patient. The process involves first determiningthe neural code 2805, which is the neural activity within the visualcortex that occurs in response to a particular image, e.g., an imagecomprising light and dark regions. The neural code 2805 represents theactivation of spatially distributed neurons of the visual cortex inresponse to the image. In addition to the spatially distributedactivation of the neurons, the neural code 2805 may also include otherparameters of the neural activity, such as the intensity, frequency,phase, etc. of the neural activations.

The neural code initially used for stimulating the neurons of the visualcortex can be derived by high frequency measurement of the neuralsignals produced by non-human primates with intact vision pathways atthe intended stimulation areas and/or optionally other areas of thevisual pathway. Utilizing neural coding obtained from non-human primateswith intact vision pathways isolates the challenge of synthesizingenough features to provide high quality information to the cortex fromthe challenge of determining existing wiring in blind animal models.Neuron-level recording allows capture of neuron-level sensed datawithout knowing the specific wiring of signals in the non-human primatesubjects.

After the neural code is determined, it is then mapped to a stimulationpattern of the visual cortex. The stimulation pattern comprises thestimulation signals that selectively activate the micro-coils of theprobe. The stimulation pattern may involve the number and position ofthe micro-coils that are activated as well as the frequency, amplitude,phase, etc. of the stimulation signals that activate the micro-coils.The stimulation pattern is determined in conjunction with a calibrationprocess that determines which neural signal spikes are caused by aparticular neuron.

Camera signals from the camera 2801 correspond to a particular imagecomponent. The neural encoder for the image component translates thecamera signals into a neural stimulation pattern that corresponds to theimage component. The visual prosthetic system applies the stimulationsignals 2810 to the micro-coil stimulators 2842 of the probes 2840according to the stimulation pattern that is intended to produce theneural code 2805 associated with the image component. For enhancedvisual restoration, the stimulation pattern may need to be adapted forthe particular patient. The neural sensor signals are obtained 2830 fromthe neural sensors 2841 and the sensor signals are used to provide afeedback signal. The initial stimulation mapping is subsequently refinedusing the feedback signal to be a patient-specific mapping using machinelearning. The machine learning is implemented and the stimulationmapping is updated accordingly until the stimulation from themicro-coils produces the neural signals that correspond to the imagecomponent. Adaptation of the stimulation pattern may involve adaptingone or both of the positions 2831 of the micro-coils activated and/orgains 2832 of the stimulation signals applied to the micro-coils and/orother parameters of the stimulation. The adapted stimulation pattern canbe stored for future use in conjunction with the particular imagecomponent.

The embodiments discussed herein can be implemented using apatient-internal device having a volume of about 0.8 cm³ capable ofoperating with less than about a 0.6° C. rise in tissue temperature. Thenumber of write channels may be between about 512 and/or the number ofread channels may be between about 256. The latency of the channels,e.g., the waiting time between the order to read/write to a neuron inthe region of interest and the beginning of the data-read/writeoperation, can be in a range of about 20 ms to about 7 ms. Isolationbetween the channels can be between about 30 dB to about 70 dB. Theregion of interest which can be sensed and/or stimulated by the neuralprobe may be an area about 0.16 cm² to about 2 cm² of the visual cortex.The region of interest can be stimulated with a resolution between about40 μm to about 20 μm.

The communication channel may have a bandwidth of about 100-500 Mbps; apower budget of between about 700 mW to about 120 mW; a link budget ofbetween about 35 to about 40 dB. The communication channel may use runlength encoding with 2:1 or 4:1 compression in some implementations.

The foregoing description of various embodiments has been presented forthe purposes of illustration and description and not limitation. Theembodiments disclosed are not intended to be exhaustive or to limit thepossible implementations to the embodiments disclosed. Manymodifications and variations are possible in light of the aboveteaching.

The invention claimed is:
 1. A vision prosthetic system, comprising: acamera configured to provide camera signals in response to images; apatient-external device comprising: a neural encoder programmed toconvert the camera signals into a neural stimulation pattern; andcommunication circuitry configured to wirelessly transmit thestimulation pattern to a patient-internal device configured to bedisposed within a cranium of a patient; the patient-internal devicecomprising: communication circuitry configured to wirelessly receive thestimulation pattern from the patient-external device; an implantableneural subsystem, comprising: a flexible substrate; a two dimensionalarray of neural probes disposed on the flexible substrate, the neuralprobes configured to stimulate and sense neurons, each neural probecomprising: an array of magnetic neural stimulators configured tomagnetically stimulate neurons; an array of neural sensors configured tosense neural signals of the neurons; and probe addressing circuitrycomprising thin film switches; and control circuitry configured tocontrol activation of the magnetic neural stimulators and neural sensorsaccording to the neural stimulation pattern via the probe addressingcircuitry.
 2. The system of claim 1, wherein the magnetic neuralstimulators comprise three dimensional coils.
 3. The system of claim 2,wherein each probe comprises about 250 to about 450 three dimensionalcoils.
 4. The system of claim 2, wherein the three dimensional coilshave a stress gradient that causes loops of the coils to curl out ofplane.
 5. The system of claim 1, wherein each probe has a threedimensional shape such that an exterior surface of the probe comprisesat least a portion of a first surface of the flexible substrate and aninterior surface of the probe comprises at least a portion of a secondsurface of the flexible substrate.
 6. The system of claim 5, wherein thethree dimensional shape of each probe is a cylinder.
 7. The system ofclaim 6, wherein each cylinder has a diameter of about 30 to about 100μm and a length of about 1.4 to about 2 mm.
 8. The system of claim 1,wherein: each probe comprises a probe area of the flexible substrate;and the flexible substrate is a multi-layered stress-engineeredstructure at least in the probe area.
 9. The system of claim 8, wherein,when laid flat, each probe area of the flexible substrate has a surfacearea of about 0.0048 cm² to about 0.032 cm².
 10. The system of claim 8,wherein a bridge of the flexible substrate attaches each probe area toother areas of the flexible substrate.
 11. The system of claim 10,wherein each probe is disposed at an angle to the other areas of theflexible substrate at the bridge.
 12. The system of claim 1, wherein theneural sensors are disposed on an exterior surface of the probe and theneural probe addressing circuitry is disposed on an interior surface ofthe probe.
 13. The subsystem of claim 1, wherein: the flexible substratehas a distal region, a proximal region, and a center region extendingbetween the distal region and the proximal region; and the neural probesare disposed at the distal region of the flexible substrate; and furthercomprising an interface area disposed at the proximal region of theflexible substrate, the interface region configured to electricallycouple the probe addressing circuitry to the control circuitry.
 14. Thesystem of claim 1, wherein the neural probes are configured to penetrateinto the visual cortex to at least the 5^(th) cortical layer.
 15. Amethod comprising: generating camera signals in response to an image;mapping the camera signals to a neural stimulation pattern thatrepresents the image; wirelessly transmitting the neural stimulationpattern to a body-implantable device that includes an array of magneticneural stimulators; and magnetically stimulating neurons of the visualcortex according to the neural stimulation pattern.
 16. The method ofclaim 15, further comprising: sensing the neurons of the visual cortexusing an array of electrical neural sensors; and adjusting the neuralstimulation pattern based on the sensing.
 17. The method of claim 15,wherein magnetically stimulating comprises magnetically stimulating thevisual cortex at a resolution of about 15 μm to about 25 μm.
 18. Themethod of claim 15, wherein magnetically stimulating comprisingcontrolling current to magnetic neural stimulators comprising threedimensional coils.
 19. The method of claim 18, wherein controllingcurrent through the three dimensional coils comprises controlling one ormore of phase, frequency, duty cycle, and amplitude of the currentpulses to the three dimensional coils.
 20. The method of claim 15,wherein magnetically stimulating the neurons comprises magneticallystimulating to predominantly activate neurons in a single orientationwhile minimally activating neurons in other orientations or notactivating neurons in other orientations.
 21. A neural modulationsystem, comprising: a patient-external device comprising: a neuralencoder programmed to convert input signals into a neural stimulationpattern; and communication circuitry configured to wirelessly transmitthe stimulation pattern to a patient-internal device configured to bedisposed within a cranium of a patient; the patient-internal devicecomprising: communication circuitry configured to wirelessly receive thestimulation pattern from the patient-external device; an implantableneural subsystem, comprising: a flexible substrate; a two dimensionalarray of neural probes disposed on the flexible substrate, the neuralprobes configured to stimulate and sense neurons, each neural probecomprising: an array of magnetic neural stimulators configured tomagnetically stimulate neurons; an array of neural sensors configured tosense neural signals of the neurons; and probe addressing circuitrycomprising thin film switches; and control circuitry configured tocontrol activation of the magnetic neural stimulators and neural sensorsaccording to the neural stimulation pattern via the probe addressingcircuitry.